RP2 + Tivozanib for Kidney Cancer

Not yet recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must be taking: Immune checkpoint inhibitors, Antiangiogenic TKIs

Must not be taking: Antivirals, Immunosuppressants

Disqualifiers: HIV, Hepatitis B/C, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: Up to 8 doses of RP2 and multiple 28-day cycles of tivozanib

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for kidney cancer that has spread and worsened despite previous treatments. It uses a modified herpes virus, RP2, to target and kill cancer cells while activating the immune system. This is combined with tivozanib, a drug that stops cancer growth and prevents new blood vessels from forming. Ideal participants have kidney cancer that has worsened after one or two rounds of prior treatment, including both immunotherapy and a specific type of cancer drug. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had systemic anticancer therapies within 4 weeks of the first dose of the study drug, and certain conditions require that anticoagulant therapies be safely stopped during the study. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that RP2, a modified herpes simplex virus designed to target tumor cells, was tested in earlier studies. In these studies, most patients experienced severe or life-threatening side effects, but researchers considered the overall safety manageable. This indicates that while side effects were common, they were generally expected and could be managed with proper care.

Tivozanib, in contrast, has undergone more extensive study and is already approved for treating kidney cancer. Its side effects are well-documented and usually manageable. Tivozanib works by blocking proteins that help tumors grow and spread.

Both treatments have been used in people before. While side effects can occur, they are generally known and can be managed by doctors. Prospective trial participants should discuss possible side effects with their doctor to understand how they might be affected. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about RP2 combined with tivozanib for kidney cancer because it offers a unique approach that differs from typical treatments like surgery, radiation, and targeted therapies such as sunitinib and pazopanib. RP2 is a modified virus designed to selectively target and destroy cancer cells when injected directly into tumors, providing a novel mechanism of action. Meanwhile, tivozanib is an oral medication that blocks signals promoting blood vessel growth in tumors, potentially enhancing the anti-cancer effects. This combination aims to effectively attack the cancer from within while cutting off its blood supply, offering hope for improved outcomes in kidney cancer management.

What evidence suggests that RP2 and tivozanib could be effective for metastatic renal cell cancer?

Research shows that RP2, a modified herpes simplex virus, targets and destroys cancer cells in kidney cancer while aiding the immune system in fighting these cells. Early studies suggest it can shrink tumors and boost the immune response. Tivozanib has delayed the progression of cancer in patients with advanced kidney cancer, with some studies reporting a delay of up to 11.9 months. In this trial, participants will receive a combination of RP2 and tivozanib, which might be a strong approach, as it directly attacks the tumor and cuts off its blood supply. ^{1 3 6 7 8}

Who Is on the Research Team?

Charles B Nguyen

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with metastatic renal cell cancer that has worsened after immunotherapy. Participants must have previously been treated with immune checkpoint inhibitors and now show disease progression.

Inclusion Criteria

Documented informed consent of the participant and/or legally authorized representative

Assent, when appropriate, will be obtained per institutional guidelines

White blood cell (WBC) count ≥ 2.0 x 10^9/L

Exclusion Criteria

History of allergy or sensitivity to study drug components or prior monoclonal antibody treatment; known hypersensitivity to Chinese hamster ovary cell products

Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study treatment. Patients who have entered the follow-up phase of an investigational study may participate if it has been 4 weeks after the last dose of the previous investigational agent

Significant bleeding event within the last 12 months that places the patient at unjustifiable risk for bleeding from intratumoral injection procedures, based on Investigator or interventional radiologist assessment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive RP2 intratumorally and tivozanib orally. RP2 is administered on days 1, 15, 29, 43, 64, 85, 106, and 127, with treatment repeating every 2 weeks for the first 4 doses and then every 3 weeks for subsequent doses. Tivozanib is taken orally once daily on days 1-21 of each 28-day cycle.

Up to 8 doses of RP2 and multiple 28-day cycles of tivozanib

Multiple visits for RP2 administration and continuous daily oral intake of tivozanib

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up includes CT scans, urine and blood sample collection, and possibly tumor biopsies.

30 days post-treatment, then every 3 months for up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• RP2
• Tivozanib

Trial Overview The trial tests RP2, a modified virus targeting tumor cells and boosting the immune response, alongside tivozanib, which inhibits proteins to stop tumor growth and new blood vessel formation. This combination aims to treat advanced kidney cancer post-immunotherapy.

How Is the Trial Designed?

Group I: Treatment (RP2, tivozanib) Experimental Treatment 5 Interventions

Patients receive RP2 intratumorally on days 1, 15, 29, 43, 64, 85, 106, and 127. Treatment repeats every 2 weeks for the first 4 doses and then every 3 weeks for subsequent doses for up to 8 doses in the absence of disease progression or unacceptable toxicity. After completion of the first course of treatment, patients who meet criteria may receive another course of RP2 intratumorally every 3 weeks for up to an additional 8 doses. Patients also receive tivozanib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT and urine and blood sample collection throughout the study. Additionally, patients may undergo tumor biopsies throughout the study.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07218692

RP2 and Tivozanib for the Treatment of Metastatic Renal ... This phase II trial tests the effect of RP2 and tivozanib in treating patients with renal cell cancer that has spread from where it first ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40203108/

Intratumoral mycobiome heterogeneity influences the ... The intratumoral mycobiome plays a crucial role in the tumor microenvironment, but its impact on renal cell carcinoma (RCC) remains unclear.

3. ir.replimune.com ir.replimune.com/static-files/e30e166c-4b8f-42cf-a764-7ac4a01f7997

Preliminary safety and efficacy results from an open-label Preliminary safety and efficacy results from an open-label, multicenter, phase 1 study of RP2 as a single agent and in.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4193312/

Intratumoral heterogeneity in kidney cancer - PMC A new study using multi-region exome sequencing has identified substantial intratumoral heterogeneity within large primary CCRCCs.

5. youtube.com youtube.com/watch?v=r5ooB6Mu-TI

Renal Cell Carcinoma TiNivo-2 Study: Patient-Reported ... In this video, we unpack the trial design, efficacy results, PRO findings, and what they mean for RCC treatment strategies. ... Kidney Cancer / ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11670916/

Real-World Outcomes in Patients With Metastatic Renal ... This study provides data to support the understanding of the real-world utilization and long-term effectiveness of 1L NIVO + IPI in patients with I/P-risk mRCC.

7. kidneycancer.org kidneycancer.org/2025-asco/

Kidney Cancer Highlights from ASCO 2025 The researchers reported a manageable and consistent safety profile although most patients – 96% – did experience severe or life-threatening ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11601845/

Safety outcomes and immunological correlates in a ... Here, we report the first prospective, non-comparative clinical trial to evaluate the feasibility, clinical benefits, and immunologic changes of combining three ...